[1]彭海燕 汪汉 唐瑾 郭思竹.多组学方法解析深静脉血栓形成的遗传背景[J].心血管病学进展,2025,(11):1044.[doi:10.16806/j.cnki.issn.1004-3934.2025.11.017]
 PENG Haiyan,WANG Han,TANG Jin,et al.Genetic Architecture of Deep Vein Thrombosis:Insights from Multi-Omics Integration[J].Advances in Cardiovascular Diseases,2025,(11):1044.[doi:10.16806/j.cnki.issn.1004-3934.2025.11.017]
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多组学方法解析深静脉血栓形成的遗传背景()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年11期
页码:
1044
栏目:
论著
出版日期:
2025-11-25

文章信息/Info

Title:
Genetic Architecture of Deep Vein Thrombosis:Insights from Multi-Omics Integration
作者:
彭海燕 汪汉 唐瑾 郭思竹
(成都市第三人民医院心内科,四川 成都 610031)
Author(s):
PENG HaiyanWANG HanTANG JinGUO Sizhu
?Department of Cardiology,The Third People s Hospital of Chengdu,Chengdu,610031Sichuan,China)
关键词:
深静脉血栓形成全基因组关联研究全转录组关联研究遗传学
Keywords:
Deep venous thrombosisGenome-wide association studyTranscriptome-wide association studyGenetics
DOI:
10.16806/j.cnki.issn.1004-3934.2025.11.017
摘要:
目的 通过多组学整合解析深静脉血栓形成(DVT)易感基因及潜在的治疗靶点,为DVT的精准防治提供遗传理论基础。方法 利用UK Biobank的DVT汇总全基因组关联研究数据,采用全转录组关联研究(TWAS)、因果基因集的精细定位、功能注释等方法探讨DVT的易感基因及可能的治疗靶点。结果 QQ图显示DVT数据无系统偏倚,高显著区域存在真实关联信号,符合DVT多基因遗传本质。TWAS分析发现7个显著基因位点,涉及凝血(FGG)、代谢(SLC19A2)、血管重塑(MMP24)及信号转导(PLRG1、TSPAN15等)通路。精细定位共筛选出14个高置信度候选因果基因(后验概率>0.6),其中MMP24、PLRG1、SLC19A2、TRPC4AP、TSPAN15为TWAS与共定位共同鉴定的基因。基因注释显示风险单核苷酸多态性位点主要位于内含子,锚定55个基因(含上述5个关键基因),富集于肝脏、血管,以及凝血-纤溶平衡通路。结论 DVT是多基因协同致病的复杂疾病,MMP24、PLRG1、SLC19A2、TRPC4AP、TSPAN15等易感基因可能成为DVT治疗的靶点。
Abstract:
Objective To explore potential susceptibility genes and therapeutic targets for deep venous thrombosis (DVT) through a multi-omics integration strategy ,providing a genetic basis for the precise prevention and treatment of DVT. Methods Utilizing the summary statistics from genome-wide association study data of DVT from the UK Biobank,this study employed methods such as transcriptome-wide association study (TWAS) ,causal gene set fine-mapping,functional annotation,and multi-marker effect testing to investigate the susceptibility genes and potential therapeutic targets of DVT. Results The QQ plot indicated no systematic bias in the DVT data ,with significant overrepresentation of true association signals in high-significance regions,consistent with the polygenic nature of DVT. TWAS analysis identified 7 significant gene loci ,involving pathways related to coagulation (FGG),metabolism (SLC19A2),vascular remodeling (MMP24),and signal transduction (PLRG1,TSPAN15,etc.). Fine mapping selected 14 high-confidence candidate causal genes (posterior probability >0.6),among which MMP24,PLRG1,SLC19A2,TRPC4AP,and TSPAN15 were jointly identified by TWAS and colocalization. FUMA annotation showed that risk SNP were primarily located in introns,anchoring 55 genes (including the 5 key genes mentioned above),enriched in the liver,blood vessels,and the coagulation-fibrinolysis balance pathway. Conclusion DVT is a complex disease caused by the synergistic effect of multiple genes. Susceptibility genes such as MMP24 ,PLRG1,SLC19A2,TRPC4AP,and TSPAN15 may serve as therapeutic targets for DVT

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更新日期/Last Update: 2026-03-06